Chemical analysis device and method

ABSTRACT

Methods and systems for chemical analysis. For instance, a device for chemical analysis of a sample includes a housing, an inlet, a pump, multiple membranes and at least one detector. The housing contains an interior chamber of the device. The inlet on the housing introduces the sample into the interior chamber. The pump is connected to the housing to form a partial vacuum in the interior chamber. The multiple membranes have different response times to different constituents of the sample. The multiple membranes include at least a first membrane and a second membrane. At least one of the first membrane and the second membrane comprises a tubular portion. The multiple membranes have different response times to different constituents of the sample. The detector is for detecting the different constituents of the sample after interaction with the multiple membranes. In addition, a method for chemical analysis of a sample. A first step includes introducing a sample to multiple membranes having different response times to different constituents of the sample. A second step includes separating the different constituents of the sample due to the different response times of the multiple membranes. A third step includes detecting the different constituents of the gas after separating with the multiple membranes.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 62/668,493, filed May 8, 2018, which is incorporated herein byreference in its entirety.

TECHNICAL FIELD

The present application generally relates to analytical systems such aschemical analyzers, and in particular to rapid response mass analysistechniques.

BACKGROUND

One of the limitations of conventional chemical analysis devices is thatthey are not readily deployable in the field, in order to allow rapidassessment of potential dangerous chemicals that may be present in amonitoring area, such as an airport, building, etc., because theyrequire fixed installations. Another limitation of conventionaltechniques is that analysis cannot be conducted rapidly because thetechniques occur in a monolithic process that takes quite some time tocomplete. A further limitation of conventional techniques relates to thefact that certain different molecules have the same profile whenanalyzed under mass spectroscopy, for instance, and are not readilydifferentiated from one another, leading to potential false positiveswhen screening or monitoring for a specific target molecule.

SUMMARY

Methods and devices for chemical analysis are presented. In one aspect,a device for chemical analysis of a sample includes a housing, an inlet,a pump, multiple membranes and at least one detector. The housingcontains an interior chamber of the device. The inlet on the housingintroduces the sample into the interior chamber. The pump is connectedto the housing to form a partial vacuum in the interior chamber. Themultiple membranes have different response times to differentconstituents of the sample. The multiple membranes include at least afirst membrane and a second membrane. At least one of the first membraneand the second membrane comprises a tubular portion. The multiplemembranes have different response times to different constituents of thesample. The detector is for detecting the different constituents of thesample after interaction with the multiple membranes.

In another aspect, a method for chemical analysis of a sample ispresented. A first step includes introducing a sample to multiplemembranes having different response times to different constituents ofthe sample. A second step includes separating the different constituentsof the sample due to the different response times of the multiplemembranes. A third step includes detecting the different constituents ofthe gas after separating with the multiple membranes.

In a further aspect, a device for chemical analysis of a sample includesa housing, an inlet, a pump, multiple membranes, at least one detector,and at least one heating element. The chamber is for receiving thesample. The multiple membranes have different response times todifferent constituents of the sample. The multiple membranes at leastpartially disposed in the chamber. The detector is disposed in thechamber and for detecting the different constituents of the sample afterinteraction with the multiple membranes. The detector includes a massspectrometer. The at least one heating element is disposed near at leastone of the multiple membranes. The at least one heating element isconfigured to heat the at least one of the multiple membranes tofacilitate different response times of the different constituents.

The above embodiments are exemplary only. Other embodiments are withinthe scope of the disclosed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the manner in which the features of the invention can beunderstood, a detailed description of the invention may be had byreference to certain embodiments, some of which are illustrated in theaccompanying drawings. It is to be noted, however, that the drawingsillustrate only certain embodiments of this invention and are thereforenot to be considered limiting of its scope, for the scope of thedisclosed subject matter encompasses other embodiments as well. Thedrawings are not necessarily to scale, emphasis generally being placedupon illustrating the features of certain embodiments of the invention.In the drawings, like numerals are used to indicate like partsthroughout the various views.

FIGS. 1-2 are schematic views of exemplary systems, in accordance withaspects set forth herein;

FIGS. 3A-3E are flowcharts of exemplary methods for analyzing chemicals,in accordance with aspects set forth herein;

FIG. 4 is a graphical representation of an image of a membrane assembly,in accordance with aspects set forth herein;

FIG. 5 is a graphical representation of an image of two membraneassemblies, in accordance with aspects set forth herein;

FIG. 6 is a graphical representation of an image of a membrane assembly,in accordance with aspects set forth herein;

FIG. 7 is a graph of the output of a chemical analyzer, in accordancewith aspects set forth herein;

FIG. 8 is a graph of the output of a chemical analyzer, in accordancewith aspects set forth herein;

FIG. 9 is a graph of the output of a chemical analyzer, in accordancewith aspects set forth herein;

FIGS. 10A-10B are graphs of the output of a chemical analyzer, inaccordance with aspects set forth herein; and

FIGS. 11A-11B are graphs of the output of a chemical analyzer, inaccordance with aspects set forth herein.

DETAILED DESCRIPTION

Embodiments of the disclosed subject matter provide techniques forchemical analysis. Other embodiments are within the scope of thedisclosed subject matter.

The present invention provides, in part, techniques and systems forrapid detection of potentially hazardous gases or volatile organiccompounds, such as chemical weapons, present in the parts per billion orparts per trillion concentration in the air. Of course, the presenttechniques are not limited to detection of chemical weapons, and may beused in industrial and other applications involving toxic chemicals. Forinstance, VX nerve gas, sarin, phosgene, mustard gas, chlorine, cyanidecompounds, etc., are all candidate chemicals that may be detectedrapidly using the techniques herein described.

Applicants have discovered that certain membranes have differentinteraction times with different molecules, and if a chemical analyzeris configured to include one or more such membranes, the differentmolecules can pass through the membranes with some degree of timeseparation. Although the time separation will not generally be perfect,enough separation may be introduced by the membranes, so that massspectroscopy or other detector techniques may be used to identify thecomponents of the gas down to parts per billion or trillion in a rapidmanner. In some examples described below, the physical separation withthe membranes may be paired with analytical techniques.

Generally stated, provided herein, in one aspect, is a device forchemical analysis of a sample includes a housing, an inlet, a pump,multiple membranes and at least one detector. The housing contains aninterior chamber of the device. The inlet on the housing introduces thesample into the interior chamber. The pump is connected to the housingto form a partial vacuum in the interior chamber. The multiple membraneshave different response times to different constituents of the sample.The multiple membranes include at least a first membrane and a secondmembrane. At least one of the first membrane and the second membranecomprises a tubular portion. The multiple membranes have differentresponse times to different constituents of the sample. The detector isfor detecting the different constituents of the sample after interactionwith the multiple membranes. In one embodiment, the detector includes amass spectrometer. In another embodiment, the device further includes achamber for introducing the sample to the multiple membranes.

In an exemplary implementation, the multiple membranes are exposed tothe sample sequentially. In another implementation, the multiplemembranes are exposed to the sample in parallel. In yet a furtherembodiment, the multiple membranes have different response times tomultiple constituents having a specific mass to charge ratio.

In one embodiment, the device further including a heating element tofacilitate the different response times of the different constituents.In another embodiment, the different constituents include differentmolecules. In a further embodiment, the detector is configured toperform a first detection of the sample after interacting with a firstof the multiple membranes to determine a preliminary result, and if thepreliminary result indicates a likelihood of an outcome, perform asecond detection of the sample after interacting with a second of themultiple membranes to determine a final result.

In a specific embodiment, the device comprises a handheld structure suchas a wand, and the wand includes the chamber, membranes, detector,heating element, battery, microcontroller, etc. In such a case, the aninlet on the wand allows for a first analysis of the sample (e.g.,collected by waving or holding the wand in the air), this first analysisbeing done rapidly. Continuing with this example, the first analysis mayrule out the presence of certain molecules, such as toxic molecules, inwhich case the analysis is completed. However, the first analysis mayindicate a potential presence of a certain molecule, and a secondanalysis would then be queued up by the inlet (or another inlet)allowing the air to interact with a second membrane that takes a longeramount of time before analysis. Such a two-stage (or, generalizing,n-stage) analysis can facilitate an operator of the handheld chemicalanalysis device to rapidly screen an area or targets.

In another aspect, a method for chemical analysis of a sample ispresented. A first step includes introducing a sample to multiplemembranes having different response times to different constituents ofthe sample. A second step includes separating the different constituentsof the sample due to the different response times of the multiplemembranes. A third step includes detecting the different constituents ofthe gas after separating with the multiple membranes.

In one embodiment of the method, separating the different constituentsof the sample includes starting and stopping a flow of the sample. Inanother embodiment, introducing the sample includes introducing thesample to a first of the multiple membranes at a first time and a secondof the multiple membranes at a second time after the first time. In afurther embodiment, the method also includes detecting a preliminaryresult after introducing the sample to the first of the multiplemembranes at the first time, and if the preliminary result indicates alikelihood of an outcome, detecting a final result after introducing thesample to the second of the multiple membranes at the second time. Byway of example, the sample may be introduced to the multiple membranesat a same time or sequentially.

In a further aspect, a device for chemical analysis of a sample includesa housing, an inlet, a pump, multiple membranes, at least one detector,and at least one heating element. The chamber is for receiving thesample. The multiple membranes have different response times todifferent constituents of the sample. The multiple membranes at leastpartially disposed in the chamber. The detector is disposed in thechamber and for detecting the different constituents of the sample afterinteraction with the multiple membranes. The detector includes a massspectrometer. The at least one heating element is disposed near at leastone of the multiple membranes. The at least one heating element isconfigured to heat the at least one of the multiple membranes tofacilitate different response times of the different constituents. Indifferent examples, the multiple membranes are exposed to the samplesequentially or in parallel. As implemented, the multiple membranes mayhave different response times to multiple constituents having a specificmass to charge ratio.

FIG. 1 schematically shows a system in which a membrane assembly 60 ispositioned at the inlet of a chemical analyzer housing 84 that includesan ion source 82 positioned at the inlet side of the housing. Theinterior of housing 84 can be pumped down to vacuum, e.g., by a pump.The ion source includes a filament (not shown) or other means forproducing a stream of electrons (e-) that are injected into anionization volume or chamber along with a sample gas 83, which includesanalytes, which passes through the membrane assembly 60 at the inlet 30of the chemical analyzer housing 84. Impact by the electrons with theincoming molecules of the sample gas 83 produces the formation ofpositive ions 85 that are caused to be accelerated into a massspectrometer mass filter 86, such as a quadrupole mass filter, in whichmasses are scanned for detection by a sensor such as an ion detector 81,having an electron multiplier or a Faraday cup, which is disposed at theopposite end of the housing 84 from the inlet 30.

In various aspects, different valves may be disposed within or near themembrane assembly 61 to allow the sample gas 83, having an analyte, or amixture or composition containing the analyte, to be applied to membraneassembly 60. The gas supply can include a pump adapted to either applypositive pressure to push material towards membrane 60 or to applynegative pressure to pull material across membrane 60.

In an example, the analytes of interest of the gas 83 are non-polarmolecules that are more soluble in the membrane 60 material than thebulk gas (e.g. air) or liquid (e.g. water). Therefore, gas 83 has a muchhigher concentration of the analyte than the original sample.

In an example, Dow Corning™ Silastic™ Q7-4750 biomedical/pharmaceuticalgrade platinum-cured silicone material may be used as a membrane.

By way of example, different membranes that have different permeationsrates for different molecules may be used either individually or incombination. By using multiple membranes, better separation may beachieved using one material compared to another. In addition, the ratethrough a first membrane material could be compared to the rate througha second membrane material, in a multiple membrane embodiment of thesystem described herein. In such a case, the relative rate differencesof passage through the two different membranes could help define themolecule, and separate the molecule from background noise from otherchemicals.

It should be noted that one goal is for separation is to stop the flowof new sample to the membrane. After stopping the flow, the gas that ispresent will go through the one or more membranes at its own rate, whichmay be dependent on the membrane composition, thickness and physicalgeometry. By contrast, if the sample flow is not stopped, new samplearriving to the membrane would just keep flowing through the membraneand separation in time would not be achieved.

Many schemes use a PDMS membrane material; non-polar molecules passthrough the PDMS membrane material quickly and polar molecules do not.

Continuing with FIG. 1, the membrane 60 is a tube that passes throughthe chamber, which is, e.g., pumped down to low pressures. A sample pumpdraws a stream of carrier fluid through the tube; the carrier fluidtransports the analyte. This system advantageously permits trapping manycontaminants at the entrance to the tube so analytes can flow throughportions of the tube downstream of the entrance. Some analytes passthrough the membrane 60 into the vacuum chamber and are detected by thedetector 81. Exemplary detectors include, but are not limited, to, massspectrometers (e.g., time of flight, quadrupole mass sensor, ion trap,or magnetic sector); photoionization detectors; optical detectors (e.g.,to detect fluorescence, absorbance, or Raman scattering); metal oxidesensors; and quartz crystal micro balances. Some sensing technologiesemploy a vacuum in the housing of the chamber and some do not. Theatmospheric composition and pressure inside the housing 84 can beselected based on the analytes to be detected and the operation of thedetector. In various aspects, the MIMS system is used as a detectionunit in a continuous process monitor (CPM). Instead of an inlet, thesystem is attached to a chamber or device in the process to bemonitored. The membrane is directly exposed to the fluid (e.g., gas) inthe chamber or device.

A heater 83 may be deployed to heat the membrane 60. For example, theheater 83 can be irradiate the membrane 60 with photons (e.g., infrared)from an LED or diode laser. This permits heating only the membrane bypicking a wavelength preferentially absorbed by the membrane, and doingso in a non-contact manner. Fast heating and cooling (no thermal mass indirect contact with membrane) can be performed. The diodes or otherradiation sources can be arranged in the vacuum system or chamber. Anynumber of sources can be used, e.g., one more-powerful source or anarray of less-powerful sources. Notably, as an advantage, the use ofmultiple membranes directly reduces the number of false positivedetection events while simultaneously reducing the total detection timerequired to sweep a given area.

Turning next to FIG. 2, a two-membrane system 200 is described. Asdepicted, a first thin membrane 261 and a second membrane 260 aredeployed in system 200. In one example, a valve (not shown) may bedeployed along the flow path from membrane 261 to membrane 260, so thatonly one membrane is exposed to the sample at a time. In other examples,both membranes may be in fluid communication with the sample at the sametime. In the example of FIG. 2, an optional second inlet 30′ is depictedin dashed lines, which, if provisioned, would allow the sample to beintroduced to both membranes 260 and 261 in parallel. This alternateembodiment would facilitate parallel introduction of the sample to bothmembranes, rather than a serial arrangement in which the inlet firstintroduces the sample to membrane 260 and then next introduces thesample to a membrane 261.

Other examples could include three, four, five, or more differentmembranes, which are connected via a system of pumps and/or valves. Themembranes may have different chemical compositions and thicknesses, andmay be designed to help separate different chemicals. The membranes maybe sequential or in parallel with the sample inlet. The membranes may beflat thin membranes like membrane 261, or may be tubular shapedmembranes like membrane 260. By way of operational overview, the systemdescribed in either FIG. 1 or FIG. 2 may be deployed within a portabletest set, having a wand for intake of atmospheric air. In such a case,the wand can include the intake port for delivering the atmosphericsample to the membrane. A person of ordinary skill in the art wouldreadily understand that one or more valves and/or pumps may be deployedin the system to allow the gas to impinge upon one or more of themembranes.

FIGS. 3A-3E are flowchart of exemplary methods for analyzing chemicals,in accordance with aspects set forth herein. Beginning with FIG. 3A, amethod 300A uses a single membrane system such as that described inFIG. 1. After the method 300A starts, at block 304 a mixture iscontinuously applied to the membrane. The mixture may include, forexample, multiple chemical components for separation. Next, at block306, the detector, such as the mass spectrometer, measures the analytesin the chamber. Assuming, for example, nothing beyond normal atmosphericcompounds are present, the system may determine that no further analysisis required, and at block 308 does not initiate separation, at block 318determines the analytes in the sample gas, and at block 320 continuesmeasuring by returning to block 304.

In another example of FIG. 3A, at block 308, based on the preliminarymeasurement while the sample gas is continuously applied to themembrane, the method 300A may determine that separation is required. Forinstance, enough signal may be detected to show the presence of somevolatile organic compounds. Upon separation being required at block 308,at block 310, the sample flow to the membrane is stopped, e.g., using avalve. By stopping the sample flow at block 310, whatever sample isalready in the system and membrane can pass through the membrane to thedetector over a period of one or more seconds.

In a further example, at block 312, the method 300A may decide thatheating the sample is desirable. For instance, the preliminarymeasurement at block 306 may indicate the possible presence of someanalytes of interest that can be further time separated by heating ofthe membrane. Next, at block 314, heat is applied to the sample and/orthe membrane. Note that in other embodiments, blocks 312 and 314 couldalso be reversed, with the heat being applied before the sample flow isstopped, depending on how fast the membrane could be heated to assist inthe separation of the analytes in the sample.

Continuing with the method 300A of FIG. 3A, at block 316 the detectormay measure the analytes in the chamber. As explained in further detailbelow, this measurement step now has the benefit of the time separationcaused by the membrane (either heated or unheated as the case may be).Thus, at block 318, the determination of analytes can be possible and/ormore accurate than without separation.

FIG. 3B depicts a method 300B, which uses the system 200 of FIG. 2,having a first (e.g., alternate) membrane 261 (FIG. 2) as well as themembrane 260 (FIG. 2). In such a case, at block 330 of the method 300B,the sample mixture is applied to the alternate membrane 261. Forinstance, membrane 261 may be a thinner membrane of the same composition(or even a different composition) as the membrane 260, and thus mayallow for less overall time separation of the mixture, but at a muchhigher speed. Then, at block 332 the analytes are measured in thechamber, and although the membrane 261 may not provide enough resolutionto determine with 99% confidence the chemical composition of the gas,enough information would be present to trigger the use of the membrane260. In such a case, at block 334, the method would proceed to block308, and the method would continue through blocks 310-320 as describedpreviously with respect to FIG. 3A. Notably, during a rapid responsedetection mode, the system could continuously loop through blocks330-334, using the thinner membrane 261, looking for an indication thatfurther action is required. For instance, the system may be deployed ina wand which emits a low volume beeping sound indicating that nothing isamiss. In such a case, as soon as (at block 332) a possibility ofspecified chemicals is detected, the wand could emit a louder beepindicating to the user that the wand should be held at that spot andthat the method is triggering separation and analysis.

Turning next to FIG. 3C, yet another embodiment of a method 300C startsand proceeds through blocks 304-308 as described above with respect tomethod 300A (FIG. 3A) or method 300B (FIG. 3B), but differs in thedetermination of required separation at block 308. In the depictedembodiment, the method 300C at block 340 then determines which ofseveral different separation membranes to use at block 340. Then, usingvalves and/or pumps, the method 300C at block 342 applies the gas samplemixture to the selected or chosen membrane. For example, based on theinitial, preliminary analysis performed at block 306, the system mayhave narrowed down the possible chemical components to a smaller subset,and can then map the possible subset to a particular membrane that ismore amenable to separation of those chemical components, and may or maynot enable heating. Subsequently, the method 300C proceeds throughblocks 312-320 as described above with respect to methods 300A (FIG. A)or method 300B (FIG. B).

In another example, FIG. 3D discloses a method 300D that starts and thenapplies the sample gas mixture to an alternate sensor at block 350. Forexample, the alternate sensor may be a different mass spectrometer, ormay be an ion mobility spectrometer, or any other analytical sensor fordetermining chemical species present in a gas or fluid. By way ofexplanation, as noted before, the multiple stage system disclosed hereinallows for an initial, or preliminary test to trigger a subsequent, moreaccurate detector. Advantageously, the combination of differentdetectors allows for a more rapid overall detection. Next, the method300D at block 352 analyzes the signal from the alternate sensor, andproceeds to block 334 to trigger separation, and proceeds through blocks304-320, as described above with respect to method 300B (FIG. 3B).

In a different implementation of automated chemical analysis, FIG. 3Edepicts a method 300E that schedules routine separations at block 360.For instance, the method 300E may periodically sample the atmosphere ora testing environment, with the test being triggered every few seconds,minutes or hours at block 362. Thereafter, the method 300E proceedsthrough steps 304-320 as described with respect to any of methods 300A(FIG. 3A), method 300B (FIG. 3B), method 300C (FIG. 3C), or method 300D(FIG. 3D).

FIG. 4 is a graphical representation of an image of a membrane assemblyincluding flange 410 and membrane 420 in the form of a tube. Membrane420 passes through flange 410 at inlets 430. The use of the term “inlet”throughout this disclosure does not restrict the direction of flowthrough inlet 430; inlets 430 can receive fluid into membrane 420 orpass fluid out of membrane 420. Membrane 420 can be arranged in a loop,as shown, or straight, or in another configuration.

FIG. 5 is a graphical representation of an image of two membraneassemblies using different membranes 420, 520. Each has a flange 410,510 and inlets 430, 530.

FIG. 6 is a graphical representation of an image of a membrane assemblyincluding a flange 610. Through the flange are arranged six inlets 530,one of which is connected to a tube and four of which are capped. Asshown, inlets 530 can be different sizes. The six inlets 530 cansupport, for example, three different membrane tubes (e.g., tubes 420,520, FIG. 5). The diameter of inlet 530 and the diameter of membrane 520do not have to be the same. In various aspects, the flange, themembranes, or an assembly of the flange and one or more membrane(s) areline-replaceable units (LRUs), i.e., they can be replaced withoutsending the system back to the factory for repair.

FIG. 7 is a graph 700 of the output of a chemical analyzer (e.g., system200 of FIG. 2) over time, demonstrating experimental results using thesystem 200 of FIG. 2 with a single analyte to explain the behavior ingeneral terms. In the example of FIG. 7, at block 710 a sample isapplied, e.g., to a loop shaped membrane. Next, at block 720, the flowof the sample is stopped. As may be seen, after the flow is stopped atblock 720, the sample signal begins to rise as the sample emerges fromthe membrane, reaches a peak and declines again. Next, at block 730 thesample is applied to both the thin membrane 261 (FIG. 2) and the loopshaped membrane 260 (FIG. 2). Immediately, the signal rises.Subsequently, the flow is stopped at block 740, and there is a delayedreaction as the signal rises to peak 701, as the analyte elutes from themembrane, and then the signal decays.

FIG. 8 is a graph 800 of the output of a chemical analyzer (e.g., system200 of FIG. 2) over time, in which two chemical compounds are applied.Toluene is depicted with curve 801 and triethyl phosphate (TEP) isdepicted with curve 802. At block 810, both continue to be applied tothe system 200. Because the toluene passes through the membrane faster,a spike is seen. Next, at block 820, the flow is stopped. Now, at block830, the TEP signal rises as it emerges from the membrane, which thetoluene signal declines.

FIG. 9 is a graph of the output of a chemical analyzer (e.g., system 200of FIG. 2) over time, in which two chemical compounds are applied. Atblock 910, the binary mixture of toluene (16.4 parts per million) andmethyl salicylate (1.4 parts per million) flow into the system 200.Curve 901 depicts the toluene signal and curve 902 depicts the methylsalicylate signal. As may be seen, the toluene signal rises rapidly andmay be possibly detected at block 920. By time t0, the toluene signaldeclines. At block 930 the sample flow is stopped. By time t1 thetoluene signal declines and at time t2 the methyl salicylate signalpeaks.

Next FIGS. 10A-11B are used to show that time separation can be combinedwith analytical approaches (e.g., algorithms) to achieve more accurateidentification of the chemicals present in a mixture gas.

To demonstrate another problem solved by the techniques set forthherein, FIG. 10A is an idealized, conceptual graph 100A of the output ofa chemical analyzer (e.g., system 200 of FIG. 2) over time, in whichthree chemical compounds are applied. In this conceptual graph 100A, anidealized detection reveals that compounds A, B and C are characterizedwith signals 101, 102 and 103, respectively. Of course, if a singlesignal (e.g., pressure) is being measured, then these three separatesignals 101-103 will not be distinct, but will instead merge into onesignal. FIG. 10B depicts the example of FIG. 10A in which the signalshave all merged together. In the graph 100B, compounds A, B and Ccombine to yield a single signal 104. The techniques set forth hereinsolve this problem, allowing the combined signal 104 of FIG. 10B to bede-convoluted to reveal the individual signals 101-103 of FIG. 10A.

Continuing along the vein of FIGS. 10A-10B, FIGS. 11A-11B are graphs ofthe output of a mass spectrometer, showing the signal intensity on theY-axis and the mass per unit charge in atomic mass units (m/z in amu) onthe X-axis. FIG. 11A shows the profile 110A of an example chemical A ofinterest. In this example, chemical A is characterized by a reading thatcomprises 30% of line 111, 12% of line 112, 25% of line 113, and 10% ofline 114.

However, if chemical A is present in a mixture of chemicals A, B and C,the output of a mass spectrometer may show profile 110B as depicted inFIG. 11B, after being sent through the system 200 of FIG. 2 andseparated using the membrane(s) thereof as described above. In such acase, further analytical or algorithmic separation may be deployed asfollows. In profile 110B, in addition to lines 111-114 noted in profile110A for chemical A, line 115 and line 116 are present as well. Further,the relative signal strength of the different lines 111-116 may be dueto the different compounds. For example, in FIG. 11B, line 115 isindicative of only chemical C, line 111 is indicative of a combinationof chemicals A and C, line 112 is indicative of a combination ofchemicals A and B, line 116 is indicative of a combination of chemicalsB and C, line 113 is indicative of only chemical A, line 114 isindicative of only chemical C, and line 117 is indicative of onlychemical B.

The algorithmic approach to separation is as follows. Data collectedfrom mass spectrometers typically consists of repeated scans over time,where each scan is an array of mass-to-charge m/z intensities. As thespectrometer is exposed to continuously changing concentrations ofmolecule fragments, it generates a two-dimensional matrix of m/zintensity values (e.g., as described in FIGS. 11A-11B). Compoundidentification algorithms examine this matrix to determine the presenceor absence of specific target chemicals. The task is typically brokendown into two separate subtasks: extraction and search.

In the first subtask, relatively pure spectra are extracted from thedata stream. Extraction (also known as deconvolution) is necessary whenseveral different molecules may be simultaneously present in thespectrometer. Some may be increasing in concentration at differentrates, while some are decreasing, and others may be part of a relativelystable background. Each molecule in the mix may have unique componentsin its m/z signature, but they may also have overlapping m/z components.Extraction attempts to correctly identify groups of related m/zintensities that correspond to separate molecules. For details on howAMDIS implements extraction see [Stein 1999]. Examples of otherapproaches are described in [Liang 1992], [Hanato 1992].

In the second subtask, relatively pure spectra have been extracted fromthe raw data matrix and each unknown extracted spectrum is compared to aset of known reference spectra (the library). Extracted spectra normallyhave no exact match in the reference library, so a similarity metric iscalculated between the unknown spectrum and each candidate in thelibrary, allowing reference spectra to be ranked in order of closestmatch. For details on how NIST implements library search see [Stein1994].

In this application we describe a potentially novel approach toextraction (or deconvolution). Existing approaches, such as those usedby AMDIS take advantage of consistencies in how compounds elute from agas chromatograph column to enter the mass spectrometer. In a GC-MS, ionintensities vary over time according to peak shapes with measurableproperties such as height, width, area, tailing etc. Compounds enteringthe spectrometer through a MIMS system in the presence of complexbackgrounds do not follow these predictable peak patterns, however. Ourapproach (tentatively called mzcc for mass/charge correlationclustering) does not depend on changes of intensity to follow anyparticular pattern.

Input to the algorithm “mzcc” is a sequence of 3 or more scans, whereeach scan lists the intensities of a series of m/z ratios. More than 3scans usually produces better results. Each of the scans must measurethe same masses so that their relative values over time can be compared.The algorithm has, for instance, three steps.

Step 1: “boundary selection” selects a time interval to analyze. Inreal-time detection applications this is typically the most recent scansavailable, so the algorithm must simply decide how many scans back intime to consider in its analysis.

Step 2: “correlation measurement: calculates e.g. the Pearsonproduct-moment correlation coefficients between each mass and everyother mass over the selected time interval. The result of thiscalculation reveals how strongly the change of intensity over time foreach ion correlates with every other ion.

Step 3: “clustering: uses an unsupervised machine learning clusteringalgorithm to group ions into those that are most closely related. Anumber of different clustering algorithms exist that can be used forthis purpose, e.g. hierarchical clustering.

Each of the three steps can be tuned in a number of different ways tooptimize results.

In step 1 the algorithm must consider how quickly the presence of targetcompounds are expected to change, relative to background compounds.Techniques such as evolving factor analysis may be used to identifyrelatively noisy or more stable regions to select an analysis boundary.Deskewing of data collected over time is important because subsequentsteps rely on an estimate of simultaneous measurements of m/zintensities.

In step 2 a threshold may be applied to the results to reduce the numberof masses under consideration. It may also be helpful to weigh therelative importance of higher masses, requiring tighter correlationsbetween lower masses than higher masses. Conversion of correlationmeasures to a distance metric used in step 3 may affect results. Optionsinclude using (1−C) or sqrt(1−C) or −log(C) or (1/C)−1

In step 3, the choice of clustering algorithm, as well as parameters tothe algorithms such as the minimum cluster sizes, minimum distancesbetween elements, etc. can have significant impact on the results. Insome cases a single mass may be present in more than one simultaneouslyoccurring compound. For example mz 127 is present in Sulfur hexafluorideand in Triethyl phosphate, but one compound may be increasing inconcentration while the other is decreasing. In this case 127 will notcorrelate well with the other masses present in either of the othercompounds. Techniques such as “soft clustering”(where each element isnot necessarily assigned to only a single cluster) may help. It is alsopossible to influence the clustering algorithm with knowledge of thetarget compounds.

The following references listed below are hereby incorporated byreference herein in their entirety:

Stein 1999: An Integrated Method for Spectrum Extraction and CompoundIdentification from GC/MS Data, Stephen E. Stein, Journal of theAmerican Society for Mass Spectrometry 1999.

Liang 1992: Heuristic evolving latent projections: resolving two-waymulticomponent data, Olav M. Kvalheim and Yi Zeng. Liang, AnalyticalChemistry 1992.

Hanato 1992: Hantao, L. W., Aleme, H. G., Pedroso, M. P., Sabin, G. P.,Poppi, R. J., & Augusto, F. (2012). Multivariate curve resolutioncombined with gas chromatography to enhance analytical separation incomplex samples: a review. Analytica chimica acta, 731, 11-23.

To the extent that the claims recite the phrase “at least one of” inreference to a plurality of elements, this is intended to mean at leastone or more of the listed elements, and is not limited to at least oneof each element. For example, “at least one of an element A, element B,and element C,” is intended to indicate element A alone, or element Balone, or element C alone, or any combination thereof. “At least one ofelement A, element B, and element C” is not intended to be limited to atleast one of an element A, at least one of an element B, and at leastone of an element C.

This written description uses examples to disclose the invention,including the best mode, and also to enable any person skilled in theart to practice the invention, including making and using any devices orsystems and performing any incorporated methods. The patentable scope ofthe invention is defined by the claims, and may include other examplesthat occur to those skilled in the art. Such other examples are intendedto be within the scope of the claims if they have structural elementsthat do not differ from the literal language of the claims, or if theyinclude equivalent structural elements with insubstantial differencesfrom the literal language of the claims.

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method, or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.), or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “service,” “circuit,” “circuitry,”“module,” and/or “system.” Furthermore, aspects of the present inventionmay take the form of a computer program product embodied in one or morecomputer readable medium(s) having computer readable program codeembodied thereon.

Any combination of one or more computer readable medium(s) may beutilized. The computer readable medium may be a computer readable signalmedium or a computer readable storage medium. A computer readablestorage medium may be, for example, but not limited to, an electronic,magnetic, optical, electromagnetic, infrared, or semiconductor system,apparatus, or device, or any suitable combination of the foregoing. Morespecific examples (a non-exhaustive list) of the computer readablestorage medium would include the following: an electrical connectionhaving one or more wires, a portable computer diskette, a hard disk, arandom access memory (RAM), a read-only memory (ROM), an erasableprogrammable read-only memory (EPROM or Flash memory), an optical fiber,a portable compact disc read-only memory (CD-ROM), an optical storagedevice, a magnetic storage device, or any suitable combination of theforegoing. In the context of this document, a computer readable storagemedium may be any tangible medium that can contain, or store a programfor use by or in connection with an instruction execution system,apparatus, or device.

Program code and/or executable instructions embodied on a computerreadable medium may be transmitted using any appropriate medium,including but not limited to wireless, wireline, optical fiber cable,RF, etc., or any suitable combination of the foregoing.

Computer program code for carrying out operations for aspects of thepresent invention may be written in any combination of one or moreprogramming languages, including an object oriented programming languagesuch as Java, Smalltalk, C++ or the like and conventional proceduralprogramming languages, such as the “C” programming language or similarprogramming languages. The program code may execute entirely on theuser's computer (device), partly on the user's computer, as astand-alone software package, partly on the user's computer and partlyon a remote computer or entirely on the remote computer or server. Inthe latter scenario, the remote computer may be connected to the user'scomputer through any type of network, including a local area network(LAN) or a wide area network (WAN), or the connection may be made to anexternal computer (for example, through the Internet using an InternetService Provider).

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems) and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer program instructions. These computer program instructions maybe provided to a processor of a general purpose computer, specialpurpose computer, or other programmable data processing apparatus toproduce a machine, such that the instructions, which execute via theprocessor of the computer or other programmable data processingapparatus, create means for implementing the functions/acts specified inthe flowchart and/or block diagram block or blocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

What is claimed is:
 1. A device for chemical analysis of a sample, thedevice comprising: a housing containing an interior chamber of thedevice; an inlet on the housing for introducing the sample into theinterior chamber; a pump connected to the housing to form a partialvacuum in the interior chamber; multiple membranes having differentresponse times to different constituents of the sample, the multiplemembranes comprising a first membrane and a second membrane, wherein atleast one of the first membrane and the second membrane comprises atubular portion; and a detector for detecting the different constituentsof the sample after interaction with the multiple membranes.
 2. Thedevice of claim 1, wherein the detector comprises a mass spectrometerand an ion source is disposed within the interior chamber.
 3. The deviceof claim 1, wherein at least another of the multiple membranes comprisesa flat portion disposed between the inlet and the interior chamber. 4.The device of claim 1, wherein the multiple membranes comprise a thirdmembrane.
 5. The device of claim 1, wherein the multiple membranes areexposed to the sample sequentially.
 6. The device of claim 1, whereinthe multiple membranes are exposed to the sample in parallel.
 7. Thedevice of claim 1, wherein the multiple membranes have differentresponse times to multiple constituents having a specific mass to chargeratio.
 8. The device of claim 1, further comprising a heating element tofacilitate the different response times of the different constituents.9. The device of claim 1, wherein the different constituents comprisedifferent molecules.
 10. The device of claim 1, wherein the detector isconfigured to perform a first detection of the sample after interactingwith a first of the multiple membranes to determine a preliminaryresult, and if the preliminary result indicates a likelihood of anoutcome, perform a second detection of the sample after interacting witha second of the multiple membranes to determine a final result.
 11. Amethod for chemical analysis of a sample, the method comprising:introducing a sample to multiple membranes having different responsetimes to different constituents of the sample; separating the differentconstituents of the sample due to the different response times of themultiple membranes; and detecting the different constituents of the gasafter separating with the multiple membranes.
 12. The method of claim11, further wherein the separating the different constituents of thesample includes starting and stopping a flow of the sample.
 13. Themethod of claim 11, wherein the introducing comprises introducing thesample to a first of the multiple membranes at a first time and a secondof the multiple membranes at a second time after the first time.
 14. Themethod of claim 13, further comprising detecting a preliminary resultafter introducing the sample to the first of the multiple membranes atthe first time, and if the preliminary result indicates a likelihood ofan outcome, detecting a final result after introducing the sample to thesecond of the multiple membranes at the second time.
 15. The method ofclaim 11, wherein the introducing comprises introducing the sample tothe multiple membranes at a same time.
 16. A device for chemicalanalysis of a sample, the device comprising: a housing containing aninterior chamber of the device; an inlet on the housing for introducingthe sample into the interior chamber; a pump connected to the housing toform a partial vacuum in the interior chamber; multiple membranes havingdifferent response times to different constituents of the sample, themultiple membranes comprising a first membrane and a second membrane,wherein at least one of the first membrane and the second membranecomprises a tubular portion; and a detector for detecting the differentconstituents of the sample after interaction with the multiplemembranes, the detector comprising a mass spectrometer; and at least oneheating element disposed near at least one of the multiple membranes,wherein the at least one heating element is configured to heat the atleast one of the multiple membranes to facilitate different responsetimes of the different constituents.
 17. The device of claim 1, whereinthe multiple membranes are exposed to the sample sequentially.
 18. Thedevice of claim 1, wherein the multiple membranes are exposed to thesample in parallel.
 19. The device of claim 1, wherein the multiplemembranes have different response times to multiple constituents havinga specific mass to charge ratio.
 20. The device of claim 1, wherein thedifferent constituents comprise different molecules.